Every year, seven million Americans arrive in emergency rooms complaining of chest pain indicating a possible heart attack. Identifying which patients are actually having a heart attack and require hospitalization can be challenging. More than 40% of emergency room chest pain patients, estimated at more than 3 million, are admitted to hospitals unnecessarily at an estimated annual cost of $10-$13 billion. These unnecessary hospitalizations may be avoided if better diagnostic tests existed for emergency room use. As pointed out in the NIH's 1997 National Heart Attack Alert Program Report on Diagnostic Technologies for Acute Cardiac Ischemia, there have been no diagnostic tests to-date that have been shown by controlled clinical trials to improve emergency room decision-making in actual practice. Unstable angina is also part of the population arriving at the emergency room. Approximately 6 out of 10,000 individuals suffer from unstable angina, or approximately 150,000 Americans.
Fatty acids are the primary source of energy for the heart muscle under normal conditions of blood flow and oxygen delivery. In ischemia, when blood flow is diminished under stress, the heart lacks an adequate supply of oxygen to utilize fatty acids efficiently. Instead, the heart shifts from fatty acid metabolism to glucose. This change occurs immediately after heart muscle ischemia. Hence, a radiolabeled fatty acid would be of value for clinical evaluation of ischemic heart disease and cardiomyopathies.
There have been numerous attempts to measure fatty acid metabolism in the heart using radiolabeled fatty acids. Although C-11 labeled fatty acids are a true tracer for fatty acids, the complicated metabolic profile and consequent pharmacokinetic modeling has kept it from being applied widely. Many fatty acids have been radiolabeled, but those that are metabolically trapped are superior to those that are metabolized. This may be analogous to a situation with 2-fluoro-2-deoxyglucose (FDG), a glucose analog, which is a more widely used than C-11 glucose because metabolic trapping leads to easier analysis by virtue of the simpler pharmacokinetic modeling. Other fatty acids have been used, for example, BMIPP ((15-p-iodophenyl)-methylpentadecanoic acid). BMIPP is an 123-iodine labeled fatty acid analog for imaging heart disease using conventional nuclear medicine cameras. BMIPP may be used to image ischemic areas of the heart soon after the ischemic event and has the added value of being able to image the ischemic muscle even several days after injury to the myocardium.
Radiolabeled fatty acids may be useful in evaluating the efficacy of beta-blocker therapy in patients with dilated cardiomyopathy (DCM) and ACE inhibitor therapy in congestive heart failure patients. These radiolabeled fatty acids have been shown to demonstrate clinical utility in the evaluation of cardiac disease, including acute myocardial infarction (AMI), unstable angina (UA), prediction of functional recovery of ischemic myocardium, prediction of future cardiac events, and assessment of therapy in patients with heart failure.
A metabolically blocked radiolabeled fatty acid may be a superior tracer to catabolizable fatty acid and therefore a Tc-99m labeled fatty acid may be of greater value than known labeled fatty acids. Early attempts to label fatty acids with Tc-99m resulted in radiopharmaceuticals that were not true fatty acid tracers. These attempts by other investigators have, in general, been directed at omega-labeled fatty acids. However, none of the omega labeled fatty acids have been shown to trace fatty acid metabolism, while some had either low heart-to-blood ratios and others exhibited low uptake in the myocardium.